This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Abstract The application of flow cytometry as a high-throughput, high information content screening platform is just beginning and has not reached its full potential. The NFCR and the University of New Mexico cytometry group will extend their long and productive history of collaboration into the technical advancement and improved application of flow-based molecular screening assays. This collaboration will extend across each of the three R&D Projects, and will evolve with the instrumental advances developed as these projects progress. In Project 1, we will use the new technical capabilities of the acoustic-focusing instrument to extend the range of flow-based screening assays into the realm of luminescence measurements. In Project 2, we will use the large-particle sorter to develop improved combinatorial library screening. In Project 3, we will develop improved multiplexed and molecular interaction screening assays based on the ability to simultaneously measure complete emission spectra and fluorescence lifetime. We will also continue our ongoing collaboration to apply the advantages of the NFCR-developed Open Reconfigurable Cytometry Acquisition System (ORCAS) digital data acquisition hardware/software to flow screening instruments developed by the UNM group. This collaboration has the potential to considerably extend the throughput, range and information content of a wide variety of cell-based and particle-based flow screening assays, directly addressing major goals of the NIH Roadmap Initiative.